Infection with Streptococcus pneumoniae can be prevented by vaccination with type-specific capsular polysaccharides. However, recipients do not respond uniformly and protective antibody levels have not been clearly defined; protection cannot be reliably predicted from antibody titers, especially for some groups at particular risk from pneumococcal infection. We propose to define opsonic requirements for several strains of S. pneumoniae and follow development of serum opsonins during infection or following vaccination. Such measurements may permit more understanding of normal host responses to pneumococcal infection as well as reasons why some recipients respond poorly to vaccination. Pneumococcal serotypes vary in pathogenicity and in opsonic requirements, whether any relationship exists between these two observations is hypothetical. However, as part of this investigation we wish to define the interactions between serotypes of varying pathogenicity and serum opsonins, including immunoglobulins and complement. We plan to study activation of complement pathways, immunoglobulin requirements thereof, and resultant opsonization, both qualitatively and quantitatively. In preliminary studies, we have identified a requirement of many pneumococcal serotypes for a clotting factor XIII - dependent serum activity in order for effective phagocytic killing to occur. In the absence of this activity, which can be absorbed from serum at O C by pneumococci and which is heat labile (56 C, 30 min), pneumococci are ingested by phagocytes, whose oxidative metabolism is activated, but bacterial killing does not occur. Electron micrographs suggest that formation of phagolysosomes is defective. We propose to identify all components of this activity and to define the mechanism of action of factor XIII in opsonization of pneumococci. In addition, we will consider function of this activity in relation to defective responses to the pneumococcal vaccine.